Infectious Diarrhoea and C. diff infections Flashcards
Microbiology of acute infectious diarrhoea
Bacterial:
- campylobacter jejuni
- salmonella typhi
- shigella spp.
- E coli
- Vibrio cholera
- C.diff
Protozoal:
- giardia intestinalis
- entamoeba histolytica
- cryptosporidium parvum
Viral
- Norovirus
- rotavirus
- adenovirus
Definition of acute infectious diarrhoea
Acute: increased freq of defecation lasting < 14 days
Diarrhoea: >= 3 loose or liquid stools OR more frequent than normal for an individual
caused by 1 or more micro-organism
epidemiology of acute infectious diarrhoea
- leading cause of death in young children
> 100,000 polyclinic visit per year
diagnosis methods for acute infectious diarrhoea
- fecal occult blood (but presence of blood may be non-specific: infection, inflammation, other causes)
- ova and parasite (under microscope)
- stool culture (takes time for result to come back)
- PCR
are diagnostic tests commonly used for acute infectious diarrhoea?
No
- diagnostic test not indicated as most case are self-limiting
Reserved for selected patients:
- severe illness (severe disease in slide 9)
- persistent fever
- bloody stools
- immunosuppression (cancer, transplant)
- unresponsive to treatment
how can we prevent acute infectious diarrhoea?
- good hand and food hygiene practices
- vaccinations:
- cholera (i.e. vibrio cholera), typhoid (.e. salmonella typhi)
- –> travelers to endemic areas
- rotavirus (in childhood immunization)
- -> infant or children 6 mths-5yrs
what are the non-pharmacologic treatment for acute infectious diarrhoea
- early re-feeding as tolerated
- easily digestible food (e.g. crackers, toast, cereal, bananas)
what are the pharmacologic treatment for acute infectious diarrhoea
- self-care: ORT, anti-peristaltic, adsorbents, probiotics
empiric abx:
- ceftriaxone 2g IV q24H (as most pt treated inpatient)
- ciprofloxacin 500mg PO BD
duration of therapy: 3-5 days
- can extend in patients with bacteremia, extra intestinal infections or immunocompromised patients
- may step down from IV to oral if the duration of therapy is extended
what are the indications to treat someone with abx for acute infectious diarrhoea
any ONE of the following:
- Severe disease
- fever with bloody diarrhoea, OR mucoid stools, OR severe abdominal pain/cramps/tenderness - Sepsis
- Immunocompromised
what are the clinical benefits of treating someone with abx when indicated
- decreases duration of symptoms (1-2 days)
- decrease morbidity and mortality
prevent complications like rehydration
what do we monitor for the therapy of acute infectious diarrhoea
- symptom resolution, clinical improvement
- further workup if persistent symptoms (e.g. PCR test)
epidemiology of Clostridioides difficile
- gram +ve, spore-forming anaerobic bacillus
- -> produces toxin A and B
- most common cause of nosocomial diarrhoea
- increase duration of hospitalisation and increase healthcare cost
Transmission:
- fecal-oral route
- contaminated environmental surfaces
- hand carriage by healthcare workers
Pathogenesis of C.difficile
- disruption of normal flora due to broad-spectrum abx or other risk factors
- C.difficile reaches the large intestine as its spores can survive the acidity of the stomach
- C.diff flourishes within colon
- the toxin A and B then causes mucosal damage
- cause bleeding, diarrhoea, cramps, fever - severe/fulminant CDI: pseudomembranous colitis, yellowish plaques form over damaged epithelium
Risk factors for C.diff
- Healthcare exposure
- prior hospitalisation
- duration of hospitalisation
- residence in nursing home or long-term care facilities (in contact w healthcare workers) - Patient-related factors
- multiple or severe comorbidities
- immunosuppression
- >65yo
- history of CDI - Pharmacotherapy
- SYSTEMIC abx (iv/oral not topical) –> increase risk with no. of agents, and duration of therapy
- high-risk abx: clindamycin, FQs, 2nd or higher gen cephalosporins
- use of gastric acid suppressive therapy (e.g. PPI)
what are the different clinical presentation of CDI
- Mild CDI
- loose stools
- abdominal cramps - Moderate CDI
- fever, nausea, malaise
- abdominal cramps and distention
- leukocytosis (elevated WBC)
- hypovolemia (sx of dehydration) - Severe or fulminant CDI
- seen in 1-3% of CDI patients
- Ileus (stops normal peristalsis movement)
- toxic megacolon, pseudomembranous colitis, perforation, death
how do we diagnose CDI
- Clinical suspicion
a. unexplained and new onset diarrhoea (i.e. at least 3 unformed stools in 24 hours)
OR
b. Radiologic evidence of ileus or toxic megacolon (diarrhoea is not seen)
- Confirmatory test or findings
a. positive stool test results for C.difficile or its toxins
OR
b. Histopathologic finding of pseudomembranous colitis (sample of colon tissue)
what are the diagnostic tests for CDI
- cultures NOT performed due to long turnaround time
thus we have other diagnostic test that have faster turnaround time, within a couple of hours:
- Nucleic acid amplification test (NAAT):
a. toxin enzyme immunoassay (EIA) - test for presence of toxin A/B
b. glutamate dehydrogenase (GDH) EIA - GDH is found inside the pathogen C.Diff
2. Polymerase chain reaction (PCR)
when do we NOT carry out the diagnostic test for CDI?
- not on asymptomatic patients (carrier of C.D.)
- dont repeat testing in < 7 days (not efficient)
- dont perform test of cure
~ >60% of patients remain positive despite successful treatment
~ so we just monitor whether the SYMPTOMS are gone
What are the infection control procedures we can do to prevent spread of CDI?
- Healthcare setting
a. practice hand hygiene
b. contact precautions recommended for 48 hours after diarrhoea resolves:
- wear gloves and gown
- wash hands with soap and water (preferred; to remove spore) after patient care - At home (patients with mild sx or those sx resolved but still taking abx):
a. wash hands with soap and water after using the bathroom
b. use separate bathroom if possible
c. clean toilets, linens, towels, clothing with bleach
before the initiation of abx for CDI, what do we need to take note of?
- if possible, discontinue concurrent abx
- increases clinical response
- decreases recurrence
(not possible if e.g. DFI treatment for 3 weeks, cannot be stopped) - Empiric CDI treatment ONLY if:
a. substantial delay (>48 hours) in diagnostics OR
b. fulminant CDI
(as diagnostic results comes back within 1-2 hours –> thus culture-directed)
for initial episode (first) of CDI for non-severe, the pharmacologic therapy recommended
non-severe =
- WBC <15 x 10^9 /L
AND
- Scr < 133 umol/L (1.5mg/dL)
- (first line)
a. Vancomycin 125mg PO QDS
b. Fidaxomicin 200mg PO BD - (alternative)
Metronidazole 400mg PO TDS
Note: for hemodialysis patient where their baseline Scr is already very high, look at the WBC levels to determine severity instead of both WBC and Scr
for initial episode (first) of CDI for severe, the pharmacologic therapy recommended
severe =
- WBC >= 15 x 10^9 /L
AND
- Scr >= 133 umol/L (1.5mg/dL)
- (first line)
a. Vancomycin 125mg PO QDS
b. Fidaxomicin 200mg PO BD
for initial episode (first) of CDI for fulminant, the pharmacologic therapy recommended
fulminant =
- hypotension OR
- ileus OR
- megacolon
- (first line)
Metronidazole 500mg IV q8H + Vancomycin 500mg PO QDS +/- Vancomycin 500mg PR QDS
treatment duration for initial episode for non-severe, severe and fulminant CDI
10 days
- may extend to 14 days if symptoms are not completely resolved
why is metronidazole not the first line anymore for non-severe CDI?
- newer date for vancomycin use in non-severe CDI:
~ increase diarrhoea resolution
~ increase clinical cure
HOWEVER, metronidazole can still be used first line for some patients locally:
- cost and
- logistical considerations (we compound IV vancomycin into oral syringes as vanco oral capsules is $$; and it will be cumbersome for outpatient)
(metronidazole commercially available as tablets)
Disadv of metronidazole:
- avoid repeated or prolong courses
~ cumulative and potentially irreversible neurotoxicity
why do we use fidaxomicin in the therapy for possibly non-severe or severe CDI?
- narrow spectrum macrocyclic abx
- inhibits transcription and protein synthesis by binding to RNA polymerase enzyme
- primarily active against gram +ve aerobes and anaerobes
~ *bactericidal against C.diff - Benefits:
- lower MIC compared to metronidazole and vancomycin
- significant post-abx effect (PAE) –> 5.5-12.5 hours
- less effect on normal Bacteroides spp (normal gut flora) in the gut
- similar cure rates as compared to vancomycin PO
~ may improve cure in immunosuppressed patients - may reduce recurrence
disadvantages of fidaxomicin, therefore preferring vancomycin PO
- very $$$
~ $30 vs $2000 for recommended treatment duration and dose - limited to severe and/or recurrent cases that are non-responsive to maximal standard therapy
C.diff treatment regimen for first recurrence
- If metronidazole was given for initial episode:
- vancomycin 125mg PO QDS x 10 days - if first line regimen for initial episode was given:
a. fidaxomicin 200mg PO BD x 10 days
b. Vancomycin PO taper:
- 125mg QDS x 10 days, 125mg BD x 1 week, 125mg daily x 1 week, 125mg every 2-3 days x 2-8 weeks
reason for vancomycin PO taper
allowing time for normal gut flora to regenerate and grow
- usually preferred over fidaxo due to cost issue
C.diff treatment regimen for second recurrence
a. fidaxomicin 200mg PO BD X 10 days
b. Vancomycin PO taper
c. Vancomycin 125mg PO QDS x 10 days, followed by rifaximin 300mg PO TDS x 20 days
d. fecal microbiota transplant
what are the monitoring parameters for CDI?
- clinical improvement typically expected in 5-7 days (diarrhoea may not go away, but stool becomes more formed, less freq diarrhoea, no fever, and lowered WBC)
- additional diagnostics or consider escalation pharmacologic treatment if poor response
- Do NOT continue C.difficile treatment for concurrent abx
~ no evidence of decrease risk of recurrence for treatment >10-14 days
~ e.g. vancomycin x 10 days along with pip-tazo for DFI. after 10 days, stop vancomycin and continue pip-tazo until remaining days of the 4 weeks is done
what are the role of probiotics in CDI
- pdts contain Saccharomyces boulardii or Lactobacillus spp.
- -> prevention of initial or recurrent CDI
- -> promote cure
- proposed mechanism:
- -> maintain/restore healthy gut flora
BUT, limitations in evidence
- -> included low-risk pt but
- -> excluded high CDI incidence
- -> variations in formation, dose, duration
CANNOT give probiotics to:
- hospitalised patients, especially immunosuppressed (as probiotics contain live virus)
Guideline says:
- not recommended for routine use to prevent or treat CDI
(outpatients can eat yogurt if they want to)
what are the role of anti-motility agents in CDI
- provides symptomatic relief for diarrhoea by inhibiting contraction of intestinal smooth muscle
- -> e.g. loperamide, diphenoxylate, atropine
- but its role in infectious diarrhoea is limited
- -> reduces bowel output, affects the ability to perform stool testing
- -> stool should come out so as to flush out the toxins
- -> assoc w poor outcomes, esp if diarrhoea is not treated appropriately
thus CDI patients SHOULD NOT be on anti-motility agents
